<i>In vivo</i>telomere dynamics of human hematopoietic stem cells

Notaro, Rosario; Cimmino, Amelia; Tabarini, Diane; Rotoli, Bruno; Luzzatto, Lucio

doi:10.1073/pnas.94.25.13782

Cited by 187 publications

(180 citation statements)

References 38 publications

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“…Previously, it was assumed that if small numbers of CD34+ cells are reinfused, these cells may have to undergo more cell divisions than larger numbers, for a similar net haematopoietic effect (Notaro et al, 1997). However, no relationship was found between the degree of TRF length shortening and the number of reinfused CD34+ cells in recent studies Wynn et al, 1999) and our data support this.…”

Section: Discussionsupporting

confidence: 45%

“…Evidence for accelerated telomere shortening after haematopoietic stem cell transplantations was found in a number of studies (Shapiro et al, 1996;Notaro et al, 1997;Akiyama et al, 1998;Ball et al, 1998;Wynn et al, 1998;Lee et al, 1999;Akiyama et al, 2000). Most data were derived from paediatric patients with haematological malignancies, and frequently mean TRF lengths after therapy were compared to mean TRF lengths of age-matched controls.…”

Section: Discussionmentioning

confidence: 99%

“…Most data were derived from paediatric patients with haematological malignancies, and frequently mean TRF lengths after therapy were compared to mean TRF lengths of age-matched controls. However, mean TRF length of nucleated blood cells has been shown to be widely variable between these controls (Notaro et al, 1997;Akiyama et al, 1998;Ball et al, 1998;Wynn et al, 1998;Lee et al, 1999). Additionally, samples were drawn at a wide range of time after PBSCT, ranging from 1.6 months to over 10 years (Akiyama et al, 1998;Wynn et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

Schröder

Wisman²,

Jong³

et al. 2001

Br J Cancer

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High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) ( n = 17), or 4 × FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT ( n = 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to ( t 0 ), 5 months after ( t 1 ) and 9 months after chemotherapy ( t 2 ); these parameters were decreased at t 1 and t 2 compared to t 0 (high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t 1 . Paired individual leukocyte samples of t 0 and t 1 showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from +0.8 to –2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t 0 and t 1 . Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment. © 2001 Cancer Research Campaign www.bjcancer.com

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Section: Discussionsupporting

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

Schröder

Wisman²,

Jong³

et al. 2001

Br J Cancer

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“…8,17 Likewise, telomere length in peripheral blood lymphocytes decreases with increasing age throughout life, at a rate of approximately 30-56 bp/year. 8,18,19 This loss occurs despite telomerase expression in hematopoietic stem cells and telomerase induction in actively dividing T and B lymphocytes. 20 When human T cells are stimulated to proliferate in vitro, high levels of telomerase are initially induced, with no significant telomere loss.…”

Section: Discussionmentioning

confidence: 99%

Measurable immune dysfunction and telomere attrition in long-term allogeneic transplant recipients

Lewis

Mullaney

Mangan

et al. 2004

Bone Marrow Transplant

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“…113 In addition, telomere erosion is well recognized to cause significant genomic instability, leading to malignant transformation. 114 …”

Section: Pathogenesismentioning

confidence: 99%

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

Morton

Saber

Baker

et al. 2017

Biology of Blood and Marrow Transplantation

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Subsequent neoplasms (SN) following hematopoietic cell transplantation (HCT) cause significant patient morbidity and mortality. Risks for specific SN types vary substantially, with particularly elevated risks for post-transplant lymphoproliferative disorders, myelodysplastic syndrome/acute myeloid leukemia, and squamous cell malignancies. This consensus document provides an overview of the current state of knowledge regarding SN after HCT and recommends priorities and approaches to overcome challenges and gaps in understanding. Numerous factors have been suggested to impact risk, including patient-related (e.g., age), primary disease-related (e.g., disease type, pre-HCT therapies), and HCT-related characteristics (e.g., type and intensity of conditioning regimen, stem cell source, development of graft-versus-host disease). However, gaps in understanding remain for each of these risk factors, particularly for patients receiving HCT in the current era due to substantial advances in clinical transplantation practices. Additionally, the influence of non-transplant-related risk factors (e.g., germline genetic susceptibility, oncogenic viruses, lifestyle factors) is poorly understood. Clarification of the magnitude of SN risks and identification of etiologic factors will require large-scale, long-term, systematic follow-up of HCT survivors with detailed clinical data. Most investigations of the mechanisms of SN pathogenesis after HCT have focused on immune drivers. Expansion of our understanding in this area will require interdisciplinary laboratory collaborations utilizing measures of immune function and availability of archival tissue from SN diagnoses. Consensus-based recommendations for optimal preventative, screening, and therapeutic approaches have been developed for certain SN after HCT, whereas for other SN, general population guidelines are recommended. Further evidence is needed to specifically tailor preventative, screening, and therapeutic guidelines for SN after HCT, particularly for unique patient populations. Accomplishment of this broad research agenda will require increased investment in systematic data collection with engagement from patients, clinicians, and interdisciplinary scientists in order to reduce the burden of SN in the rapidly growing population of HCT survivors.

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In vivotelomere dynamics of human hematopoietic stem cells

Cited by 187 publications

References 38 publications

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

Measurable immune dysfunction and telomere attrition in long-term allogeneic transplant recipients

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

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